Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

Laetitia Canini, Swati DebRoy, Zoe Mariño, Jessica Maral Conway, Gonzalo Crespo, Miquel Navasa, Massimo D'Amato, Peter Ferenci, Scott J. Cotler, Xavier Forns, Alan S. Perelson, Harel Dahari

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Methods: Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to final effectiveness [εmax]) was fitted to viral kinetic data. Results: Baseline viral load and age were significantly associated with the severity of liver disease (P<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline in patients with less severe liver disease. The εmax was significantly (P≤0.032) associated with increasing severity of liver disease (non-cirrhotic εmax [SE]=0.86 [0.05], compensated cirrhotic εmax=0.69 [0.06] and decompensated cirrhotic εmax=0.59 [0.1]). The second phase decline slope was not significantly different among groups (mean 1.88 ±0.15 log10 IU/ml/week, P=0.75) as was the rate of change of SIL effectiveness (k=2.12/day [SE=0.18/day]). HCV-infected cell loss rate (δ [SE]=0.62/ day [0.05/day]) was high and similar among groups. Conclusions: The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalAntiviral Therapy
Volume20
Issue number2
DOIs
StatePublished - Jan 1 2015

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Liver Diseases
Fibrosis
Viral Load
Liver Transplantation
Antiviral Agents
silybin
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Canini, Laetitia ; DebRoy, Swati ; Mariño, Zoe ; Conway, Jessica Maral ; Crespo, Gonzalo ; Navasa, Miquel ; D'Amato, Massimo ; Ferenci, Peter ; Cotler, Scott J. ; Forns, Xavier ; Perelson, Alan S. ; Dahari, Harel. / Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy. In: Antiviral Therapy. 2015 ; Vol. 20, No. 2. pp. 149-155.
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abstract = "Background: HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Methods: Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to final effectiveness [εmax]) was fitted to viral kinetic data. Results: Baseline viral load and age were significantly associated with the severity of liver disease (P<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline in patients with less severe liver disease. The εmax was significantly (P≤0.032) associated with increasing severity of liver disease (non-cirrhotic εmax [SE]=0.86 [0.05], compensated cirrhotic εmax=0.69 [0.06] and decompensated cirrhotic εmax=0.59 [0.1]). The second phase decline slope was not significantly different among groups (mean 1.88 ±0.15 log10 IU/ml/week, P=0.75) as was the rate of change of SIL effectiveness (k=2.12/day [SE=0.18/day]). HCV-infected cell loss rate (δ [SE]=0.62/ day [0.05/day]) was high and similar among groups. Conclusions: The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.",
author = "Laetitia Canini and Swati DebRoy and Zoe Mari{\~n}o and Conway, {Jessica Maral} and Gonzalo Crespo and Miquel Navasa and Massimo D'Amato and Peter Ferenci and Cotler, {Scott J.} and Xavier Forns and Perelson, {Alan S.} and Harel Dahari",
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Canini, L, DebRoy, S, Mariño, Z, Conway, JM, Crespo, G, Navasa, M, D'Amato, M, Ferenci, P, Cotler, SJ, Forns, X, Perelson, AS & Dahari, H 2015, 'Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy', Antiviral Therapy, vol. 20, no. 2, pp. 149-155. https://doi.org/10.3851/IMP2806

Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy. / Canini, Laetitia; DebRoy, Swati; Mariño, Zoe; Conway, Jessica Maral; Crespo, Gonzalo; Navasa, Miquel; D'Amato, Massimo; Ferenci, Peter; Cotler, Scott J.; Forns, Xavier; Perelson, Alan S.; Dahari, Harel.

In: Antiviral Therapy, Vol. 20, No. 2, 01.01.2015, p. 149-155.

Research output: Contribution to journalArticle

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T1 - Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy

AU - Canini, Laetitia

AU - DebRoy, Swati

AU - Mariño, Zoe

AU - Conway, Jessica Maral

AU - Crespo, Gonzalo

AU - Navasa, Miquel

AU - D'Amato, Massimo

AU - Ferenci, Peter

AU - Cotler, Scott J.

AU - Forns, Xavier

AU - Perelson, Alan S.

AU - Dahari, Harel

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. Methods: Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to final effectiveness [εmax]) was fitted to viral kinetic data. Results: Baseline viral load and age were significantly associated with the severity of liver disease (P<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline in patients with less severe liver disease. The εmax was significantly (P≤0.032) associated with increasing severity of liver disease (non-cirrhotic εmax [SE]=0.86 [0.05], compensated cirrhotic εmax=0.69 [0.06] and decompensated cirrhotic εmax=0.59 [0.1]). The second phase decline slope was not significantly different among groups (mean 1.88 ±0.15 log10 IU/ml/week, P=0.75) as was the rate of change of SIL effectiveness (k=2.12/day [SE=0.18/day]). HCV-infected cell loss rate (δ [SE]=0.62/ day [0.05/day]) was high and similar among groups. Conclusions: The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

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